Please use this identifier to cite or link to this item:
Title: Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk
Author: Haas, Cameron B.
Su, Yu-ru
Petersen, Paneen
Wang, Xiaoliang
Bien, Stephanie A.
Lin, Yi
Albanes, Demetrius
Weinstein, Stephanie J.
Jenkins, Mark A.
Figueiredo, Jane C.
Newcomb, Polly A.
Casey, Graham
Le Marchand, Loic
Campbell, Peter T.
Moreno Aguado, Víctor
Potter, John D.
Sakoda, Lori C.
Slattery, Martha L.
Chan, Andrew T.
Li, Li
Giles, Graham G.
Milne, Roger L.
Gruber, Stephen B.
Rennert, Gad
Woods, Michael O.
Gallinger, Steven
Berndt, Sonja
Hayes, Richard B.
Huang, Wen-Yi
Wolk, Alicja
White, Emily
Nan, Hongmei
Nassir, Rami
Lindor, Noralane M.
Lewinger, Juan P.
Kim, Andre E.
Conti, David
Gauderman, W. James
Buchanan, Daniel D.
Peters, Ulrike
Hsu, Li
Keywords: Càncer colorectal
Expressió gènica
Colorectal cancer
Gene expression
Issue Date: 7-Nov-2022
Publisher: Springer Science and Business Media LLC
Abstract: Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (G x E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G x E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E-4), and Aspartylglucosaminidase (AGA: p = 4.5E-4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.
Note: Reproducció del document publicat a:
It is part of: Scientific Reports, 2022, vol. 12, issue. 1
Related resource:
ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
s41598-022-23451-y (1).pdf1.02 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons